Composition for preventing or treating cervical cancer having human papillomavirus plasmodium and immunity enhancer

Abstract

A composition for preventing or treating cervical cancer comprising a human papillomavirus plasmodium and an immunity enhancer is provided. A fusion protein including a fusion polypeptide recombined to transform a 3D structure of E6 and E7, which are antigens against types 16 and 18 human papillomavirus (HPV), a signal peptide for secreting the fusion polypeptide outside the cells and an immunity enhancer peptide present in an individual is also provided. The fusion protein may be useful in treating HPV-triggered tumors by inducing an immune response specific to the antigens against the HPV types 16 and 18.

What is claimed is: 
     
       1. A polynucleotide comprising from the 5′ end to the 3′ end a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 1 to 85 of an E6 protein of HPV serotype 16, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 1 to 65 of an E7 protein of HPV serotype 16, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 71 to 158 of an E6 protein of HPV serotype 16, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 51 to 98 of an E7 protein of HPV serotype 16, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 1 to 85 of an E6 protein of HPV serotype 18, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 1 to 65 of an E7 protein of HPV serotype 18, a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 71 to 158 of an E6 protein of HPV serotype 18, and a nucleic acid sequence encoding an amino acid sequence corresponding to amino acids 51 to 105 of an E7 protein of HPV serotype 18. 
     
     
       2. The polynucleotide of  claim 1 , further comprising a nucleic acid sequence encoding an immunity enhancer peptide. 
     
     
       3. The polynucleotide of  claim 2 , wherein the immunity enhancer peptide is selected from a CD40 ligand, an fms-like tyrosine kinase-3 (Flt3) ligand, a flagellin, and an OX40. 
     
     
       4. The polynucleotide of  claim 2 , further comprising a nucleic acid sequence encoding a signal peptide. 
     
     
       5. The polynucleotide of  claim 4 , wherein the signal peptide is selected from a tissue plasminogen activator (“tPa”) signal peptide, a Herpes Simplex Virus glycoprotein Ds (“HSV gDs”) signal peptide, and a growth hormone signal peptide. 
     
     
       6. The polynucleotide of  claim 1 , which is codon optimized. 
     
     
       7. The polynucleotide of  claim 2 , wherein the nucleic acid sequence encoding the immunity enhancer peptide is codon optimized. 
     
     
       8. The polynucleotide of  claim 4 , wherein the nucleic acid sequence encoding the signal peptide is codon optimized. 
     
     
       9. A vector comprising the polynucleotide of  claim 6 . 
     
     
       10. The vector of  claim 9 , which is a plasmid. 
     
     
       11. An isolated host cell comprising the vector of  claim 9 . 
     
     
       12. A composition comprising the polynucleotide of  claim 1  and a pharmaceutically allowable carrier. 
     
     
       13. A fusion protein encoded by the polynucleotide of  claim 1 . 
     
     
       14. A fusion protein comprising from the N-terminus to the C-terminus an amino acid sequence corresponding to amino acids 1 to 85 of an E6 protein of Human papilloma virus (HPV) serotype 16, an amino acid sequence corresponding to amino acids 1 to 65 of an E7 protein of HPV serotype 16, an amino acid sequence corresponding to amino acids 71 to 158 of an E6 protein of HPV serotype 16, an amino acid sequence corresponding to amino acids 51 to 98 of an E7 protein of HPV serotype 16, an amino acid sequence corresponding to amino acids 1 to 85 of an E6 protein of HPV serotype 18, an amino acid sequence corresponding to amino acids 1 to 65 of an E7 protein of HPV serotype 18, an amino acid sequence corresponding to amino acids 71 to 158 of an E6 protein of HPV serotype 18, and an amino acid sequence corresponding to amino acids 51 to 105 of an E7 protein of HPV serotype 18. 
     
     
       15. The fusion protein of  claim 13 , further comprising an immunity enhancer peptide. 
     
     
       16. The fusion protein of  claim 13 , further comprising a signal peptide. 
     
     
       17. A method of inducing a T cell immune response to an individual in need thereof comprising administering the polynucleotide of  claim 1  to the individual, wherein the T cell immune response is against an E6 protein of HPV serotype 16, an E7 protein of HPV serotype 16, an E6 protein of HPV serotype 18, or an E7 protein of HPV serotype 18. 
     
     
       18. A method of treating a tumor triggered by HPV in an individual in need thereof comprising administering an effective amount of a composition comprising the polynucleotide of  claim 1  to the individual. 
     
     
       19. The method of  claim 18 , wherein the tumor is cervical cancer and wherein the tumor volume is reduced after the administration.